tbuckley/cabot-search huggingface dataset:
Liquid Core Nanoparticle with High Deformability Enables Efficient Penetration across Biological Barriers
Authors: Chun Wang, Jian Xiao, Xinyue Hu, Qi Liu, Yadan Zheng, Ziyao Kang, Dongsheng Guo, Linqi Shi, Yang Liu
Journal: Advanced Healthcare Materials (2022)

Biological barriers significantly limit the delivery efficiency of drug delivery systems, resulting in undesired therapeutic effects. When designing a delivery system with optimized penetration behavior across the biological barriers, mechanical properties, such as deformability, are emerging as important parameters that need to be considered, although they are usually neglected in current research. Herein, a liquid core nanoparticle (LCN) composed of a polymer-encapsulated edible oil droplet is demonstrated. Owing to the unique structure in which the liquid oil core is encapsulated by a layer of highly hydrophilic and cross-linked polymer, the LCN exhibits high mechanical softness, making it deformable under external forces. With high deformability, LCNs can effectively penetrate through several important biological barriers including deep tumor tissue, blood-brain barriers, mucus layers, and bacterial biofilms. Moreover, the potential of the LCN as a drug delivery system is also demonstrated by the loading and release of several clinical drugs. With the capability of penetrating biological barriers and delivering drugs, LCN provides a potential platform for disease treatments, particularly for those suffering from inadequate drug penetration.
Special Delivery—Metabolic Bariatric Surgery as a Key Component of Maternal-Fetal Health Care
Authors: Tayler James, Kamran Samakar, Matthew J. Martin
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Increased 68Ga-DOTATATE Uptake in Supraclavicular Brown Adipose Tissue
Authors: Li Li, Guannan Li, Rong Tian, Guohua Shen
Journal: Clinical Nuclear Medicine (2022)

Characterization of brown adipose tissue (BAT) 18F-FDG uptake has been well reported; however, 68Ga-DOTA-conjugated somatostatin receptor targeting peptides uptake in BAT is rarely documented. Herein, we report an interesting case of increased 68Ga-DOTATATE uptake in supraclavicular BAT in a young boy with paroxysmal hypertension. The low body mass index and increased perfusion of BAT in response to cold may be significant influencing factors.
Patterned Duplex Fabric Based on Genetically Modified Spidroin for Smart Wound Management
Authors: Baoyang Lin, Liquan Yuan, Bingbing Gao, Bingfang He
Journal: Advanced Healthcare Materials (2022)

Abstract The treatment of diabetic wounds remains a great challenge for the medical community. Here, a smart patterned DNA double helix (duplex)‐like fabric based on genetically modified spider silk protein (PDF‐S) which is inspired by soft plant tendrils, is proposed for diabetic wound treatment. Benefiting from spider silk protein (spidroin); PDF‐S is equipped with high strength; high toughness, and excellent biocompatibility. Notably, the fabric crimped through the biomimetic DNA double‐helix‐like structure can effectively adapt to tensile impact and the maximum stretch rate reaches 1500%. A pattern‐based microfluidic channel of PDF‐S allowed wound secretion to flow spontaneously through the channel. Meanwhile; due to the optical properties of the introduced photonic crystal structure; PDF‐S is equipped with fluorescence enhancement properties; enabling PDF‐S to display color‐sensitive behavior suitable for wound monitoring and guiding clinical treatment. In addition, to enable sensitive motion monitoring, microelectronic circuits are integrated on the surface of the PDF‐S. These unique material features suggest that this study will lead to a new generation of biomimetic artificial spider silk materials for design and application in the biomedical field.
Superiority of 68Ga-FAPI-04 in Delineation of Soft Tissue and Liver Metastases in Chromophobe Renal Cell Carcinoma for Restaging
Authors: Fei Xie, Lilan Fu, Wenlan Zhou
Journal: Clinical Nuclear Medicine (2022)

Abstract Chromophobe renal cell carcinoma (RCC) is a rare tumor. We described findings of 18 F-FDG PET/CT and 68 Ga-FAPI-04 PET/CT of metastatic chromophobe RCC in a 56-year-old woman. 68 Ga-FAPI-04 PET/CT demonstrated that the metastatic lesions in the liver, left posterior abdominal wall, and the left waist had intense uptake of 68 Ga-FAPI-04, which was higher than that of 18 F-FDG on 18 F-FDG PET/CT. 68 Ga-FAPI-04 PET/CT also delineated the metastatic lesions more clearly than 18 F-FDG PET/CT. This case highlights 68 Ga-FAPI-04 PET/CT may be promising in restaging of chromophobe RCC.
Deciphering lipid dysregulation in ALS: from mechanisms to translational medicine
Authors: Ira Agrawal, Yong Shan Lim, Shi-Yan Ng, Shuo-Chien Ling
Journal: Translational Neurodegeneration (2022)

Abstract Lipids, defined by low solubility in water and high solubility in nonpolar solvents, can be classified into fatty acids, glycerolipids, glycerophospholipids, sphingolipids, and sterols. Lipids not only regulate integrity and fluidity of biological membranes, but also serve as energy storage and bioactive molecules for signaling. Causal mutations in SPTLC1 (serine palmitoyltransferase long chain subunit 1) gene within the lipogenic pathway have been identified in amyotrophic lateral sclerosis (ALS), a paralytic and fatal motor neuron disease. Furthermore, lipid dysmetabolism within the central nervous system and circulation is associated with ALS. Here, we aim to delineate the diverse roles of different lipid classes and understand how lipid dysmetabolism may contribute to ALS pathogenesis. Among the different lipids, accumulation of ceramides, arachidonic acid, and lysophosphatidylcholine is commonly emerging as detrimental to motor neurons. We end with exploring the potential ALS therapeutics by reducing these toxic lipids.
Flexible and Zwitterionic Fluorinated Hydrogel Scaffold with High Fluorine Content for Noninvasive <sup>19</sup>F Magnetic Resonance Imaging under Ultrahigh Scanning Resolution
Authors: Zujian Feng, Qinghua Li, Shuangyang Li, Yushan Zhang, Xiang Liu, Chuangnian Zhang, Anjie Dong, Deling Kong, Weiwei Wang, Pingsheng Huang
Journal: Advanced Healthcare Materials (2022)

The imaging of hydrogel scaffolds by 19 F magnetic resonance imaging (MRI) represents an attractive tool for straightforward and noninvasive monitoring of their morphology and in vivo fate. However, their further applications are significantly limited by a dilemma of insufficient signal resolution with low 19 F content, and/or hydrophobic aggregation of fluorine moieties-induced signal attenuation with high 19 F content. Herein, a novel label-free fluorinated hydrogel (PFCB) is fabricated with high fluorine content to realize noninvasive monitoring through 19 F MRI under ultrahigh scanning resolution (1 mm of scanning thickness). The integration of a zwitterionic unit into each fluorine moiety completely overcame the hydrophobic aggregation-induced signal attenuation, manifesting as high 19 F content and imaging performance. Importantly, 3D reconstruction of the PFCB hydrogel in vivo can be facilely and accurately performed with background free signals, providing detailed biological information of the implanted hydrogel. Additionally, PFCB hydrogel showed adjustable and high mechanical performance, and exhibited minimum foreign body reaction after implantation. As a proof of concept, PFCB hydrogel could be further applied as gel electrodes and wireless flexible sensors for healthcare monitoring. Overall, such label-free fluorinated PFCB hydrogel is an ideal flexible scaffold for eventual clinical applications integrating 19 F MRI-guided unequivocally 3D reconstruction and healthcare monitoring.
FDG PET/CT Aiding in Early Diagnosis of Central Pontine Myelinolysis
Authors: Varun Singh Dhull, Suraj Shinde, Nikhil Sane, Sandeep Avinash Bhavsar, Manoranjan Chowhan
Journal: Clinical Nuclear Medicine (2022)

Abstract We report a 70-year-old man with central pontine myelinolysis who presented in the emergency department with recent onset altered sensorium and tremors (Glasgow Coma Scale score, 13). Laboratory findings revealed hyponatremia and hypokalemia. MRI brain was unremarkable. Subsequently, patient was referred for FDG PET/CT to rule out malignancy or paraneoplastic syndrome. FDG PET revealed focal radiotracer uptake in the pons without any underlying CT abnormality consistent with central pontine myelinolysis, thus aiding in early diagnosis where conventional imaging modality was unremarkable.
Can System Solutions Be Scaled to Control High Blood Pressure and Lipids?
Authors: Neha J. Pagidipati, Eric D. Peterson
Journal: JAMA Cardiology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
68Ga-FAPI and 18F-FDG PET/CT Images of a Patient With Rosai-Dorfman Disease With Liver Involvement
Authors: Zhenying Chen, Qianqian Xue, Yun Yang, Hu Shun, Weibing Miao
Journal: Clinical Nuclear Medicine (2022)

Abstract Rosai-Dorfman disease is a rare non-Langerhans cell histiocytosis that is histopathologically characterized by the accumulation of CD68-positive and S100-positive histiocytes. The pathological changes are mostly discovered in lymph nodes. We report a case of Rosai-Dorfman disease with liver and bone marrow involvement. In this case, 18 F-FDG PET/CT revealed FDG avidity in multiple lymph nodes, liver, and bone marrow. 68 Ga-FAPI PET/CT showed higher uptake of 68 Ga-FAPI than that of 18 F-FDG in the same lesions. The findings of 68 Ga-FAPI PET/CT in this patient highlighted the potential value of 68 Ga-FAPI for staging in Rosai-Dorfman disease.
Primary Neuroendocrine Carcinoma of Pineal Gland With Extensive Meningeal Metastasis Detected by 18F-NOTATATE PET/CT
Authors: Yujiao Deng, Limeng He, Hanyan Gao, Ying Deng, Wei Zhang
Journal: Clinical Nuclear Medicine (2022)

Abstract Primary neuroendocrine tumor of the pineal gland is a rare disease. A 44-year-old woman with right cerebellopontine angle metastatic small cell neuroendocrine carcinoma underwent 18 F-FDG and 18 F-NOTATATE PET/CT scans. 18 F-NOTATATE PET/CT showed intense uptake in the pineal gland lesions and multiple foci of intense focus of uptake in the intracranial leptomeningeal and whole spinal canal. However, the lesions are less impressive on 18 F-FDG PET/CT.
Impact of universal testing and treatment on sexual risk behaviour and herpes simplex virus type 2: a prespecified secondary outcomes analysis of the HPTN 071 (PopART) community-randomised trial
Authors: Ethan Wilson, Deborah Donnell, Timothy Skalland, Sian Floyd, Ayana Moore, Nomtha Bell-Mandla, Justin Bwalya, Nkatya Kasese, Rory Dunbar, Kwame Shanaube, Barry Kosloff, Oliver Laeyendecker, Yaw Agyei, Graeme Hoddinott, Peter Bock, Sarah Fidler, Richard Hayes, Helen Ayles
Journal: The Lancet HIV (2022)
COP27 Climate Change Conference: urgent action needed for Africa and the world
Authors: Lukoye Atwoli, Gregory E. Erhabor, Aiah A. Gbakima, Abraham Haileamlak, Jean-Marie Kayembe Ntumba, James Kigera, Laurie Laybourn-Langton, Bob Mash, Sahar Yassien Mohammad, Joy Muhia, Fhumulani Mavis Mulaudzi, David Ofori-Adjei, Friday Okonofua, Arash Rashidian, Maha El-Adawy, Siaka Sidibe, Abdelmadjid Snouber, James Tumwine, Paul Yonga, Lilia Zakhama, Chris Zielinski
Journal: Journal of the Royal Society of Medicine (2022)
Fluorouracil and dose-dense adjuvant chemotherapy in patients with early-stage breast cancer (GIM2): end-of-study results from a randomised, phase 3 trial
Authors: Lucia Del Mastro, Francesca Poggio, Eva Blondeaux, Sabino De Placido, Mario Giuliano, Valeria Forestieri, Michelino De Laurentiis, Adriano Gravina, Giancarlo Bisagni, Anita Rimanti, Anna Turletti, Cecilia Nisticò, Angela Vaccaro, Francesco Cognetti, Alessandra Fabi, Simona Gasparro, Ornella Garrone, Maria Grazia Alicicco, Ylenia Urracci, Mauro Mansutti, Paola Poletti, Pierpaolo Correale, Claudia Bighin, Fabio Puglisi, Filippo Montemurro, Giuseppe Colantuoni, Matteo Lambertini, Luca Boni, M Venturini, A Abate, S Pastorino, G Canavese, C Vecchio, M Guenzi, M Lambertini, A Levaggi, S Giraudi, V Accortanzo, C.A. Floris, E Aitini, G Fornari, S Miraglia, G Buonfanti, M.C. Cherchi, F Petrelli, A Vaccaro, E Magnolfi, A Contu, R Labianca, A Parisi, C Basurto, F Cappuzzo, M Merlano, S Russo, M Mansutti, E Poletto, M Nardi, D Grasso, A Fontana, L Isa, M Comandè, L Cavanna, S Iacobelli, S Milani, G Mustacchi, S Venturini, A.F. Scinto, M.G. Sarobba, P Pugliese, A Bernardo, I Pavese, M Coccaro, B Massidda, M.T. Ionta, A Nuzzo, L Laudadio, V Chiantera, R Dottori, M Barduagni, F Castiglione, F Ciardiello, V Tinessa, A Ficorella, L Moscetti, I Vallini, G Giardina, R Silva, M Montedoro, E Seles, F Morano, G Cruciani, V Adamo, A Pancotti, V Palmisani, A Ruggeri, E Cammilluzzi, F Carrozza, M D'Aprile, M Brunetti, P Gallotti, E Chiesa, F Testore, A D'Arco, A Ferro, A Jirillo, M Pezzoli, G Scambia, C Iacono, P Masullo, G Tomasello, G Gandini, A Zoboli, C Bottero, M Cazzaniga, G Genua, S Palazzo, M D'Amico, D Perrone
Journal: The Lancet Oncology (2022)
Differential symptomology of possible and confirmed Ebola virus disease infection in the Democratic Republic of the Congo: a retrospective cohort study
Authors: Justus Nsio, Denis-Luc Ardiet, Rebecca M Coulborn, Emmanuel Grellety, Manuel Albela, Francesco Grandesso, Richard Kitenge, Dolla L Ngwanga, Bibiche Matady, Guyguy Manangama, Mathias Mossoko, John Kombe Ngwama, Placide Mbala, Francisco Luquero, Klaudia Porten, Steve Ahuka-Mundeke
Journal: The Lancet Infectious Diseases (2022)
Cancer risk with topical calcineurin inhibitors, pimecrolimus and tacrolimus, for atopic dermatitis: a systematic review and meta-analysis
Authors: Niveditha Devasenapathy, Alexandro Chu, Melanie Wong, Archita Srivastava, Renata Ceccacci, Clement Lin, Margaret MacDonald, Aaron Wen, Jeremy Steen, Mitchell Levine, Lonnie Pyne, Lynda Schneider, Derek K Chu
Journal: The Lancet Child & Adolescent Health (2022)
Kaurenoic acid nanocarriers regulates cytokine production and inhibit breast cancer cell migration
Authors: Kézia Cristine Barbosa Ferreira, Ana Beatriz Caribé Dos Santos Valle, Ana Cristina Moura Gualberto, Davi Trombini Aleixo, Lívia Mara Silva, Milena Maciel Santos, Danilo de Souza Costa, Letícia Ludmilla Oliveira, Jacy Gameiro, Guilherme Diniz Tavares, Ademar Alves da Silva Filho, José Otávio do Amaral Corrêa, Frederico Pittella
Journal: Journal of Controlled Release (2022)
Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies
Authors: Abdullah O. Khan, Antonio Rodriguez-Romera, Jasmeet S. Reyat, Aude-Anais Olijnik, Michela Colombo, Guanlin Wang, Wei Xiong Wen, Nikolaos Sousos, Lauren C. Murphy, Beata Grygielska, Gina Perrella, Christopher B. Mahony, Rebecca E. Ling, Natalina E. Elliott, Christina Simoglou Karali, Andrew P. Stone, Samuel Kemble, Emily A. Cutler, Adele K. Fielding, Adam P. Croft, David Bassett, Gowsihan Poologasundarampillai, Anindita Roy, Sarah Gooding, Julie Rayes, Kellie R. Machlus, Bethan Psaila
Journal: Cancer Discovery (2022)

Abstract A lack of models that recapitulate the complexity of human bone marrow has hampered mechanistic studies of normal and malignant hematopoiesis and the validation of novel therapies. Here, we describe a step-wise, directed-differentiation protocol in which organoids are generated from induced pluripotent stem cells committed to mesenchymal, endothelial, and hematopoietic lineages. These 3D structures capture key features of human bone marrow—stroma, lumen-forming sinusoids, and myeloid cells including proplatelet-forming megakaryocytes. The organoids supported the engraftment and survival of cells from patients with blood malignancies, including cancer types notoriously difficult to maintain ex vivo. Fibrosis of the organoid occurred following TGFβ stimulation and engraftment with myelofibrosis but not healthy donor–derived cells, validating this platform as a powerful tool for studies of malignant cells and their interactions within a human bone marrow–like milieu. This enabling technology is likely to accelerate the discovery and prioritization of novel targets for bone marrow disorders and blood cancers. Significance: We present a human bone marrow organoid that supports the growth of primary cells from patients with myeloid and lymphoid blood cancers. This model allows for mechanistic studies of blood cancers in the context of their microenvironment and provides a much-needed ex vivo tool for the prioritization of new therapeutics. See related commentary by Derecka and Crispino, p. 263. This article is highlighted in the In This Issue feature, p. 247
<i>ETV6</i> Deficiency Unlocks ERG-Dependent Microsatellite Enhancers to Drive Aberrant Gene Activation in B-Lymphoblastic Leukemia
Authors: Rohan Kodgule, Joshua W. Goldman, Alexander C. Monovich, Travis Saari, Athalee R. Aguilar, Cody N. Hall, Niharika Rajesh, Juhi Gupta, Shih-Chun A. Chu, Li Ye, Aishwarya Gurumurthy, Ashwin Iyer, Noah A. Brown, Mark Y. Chiang, Marcin P. Cieslik, Russell J.H. Ryan
Journal: Blood Cancer Discovery (2022)

Distal enhancers play critical roles in sustaining oncogenic gene-expression programs. We identify aberrant enhancer-like activation of GGAA tandem repeats as a characteristic feature of B-cell acute lymphoblastic leukemia (B-ALL) with genetic defects of the ETV6 transcriptional repressor, including ETV6-RUNX1+ and ETV6-null B-ALL. We show that GGAA repeat enhancers are direct activators of previously identified ETV6-RUNX1+/- like B-ALL "signature" genes, including the likely leukemogenic driver EPOR. When restored to ETV6-deficient B-ALL cells, ETV6 directly binds to GGAA repeat enhancers, represses their acetylation, downregulates adjacent genes, and inhibits B-ALL growth. In ETV6-deficient B-ALL cells, we find that the ETS transcription factor ERG directly binds to GGAA microsatellite enhancers and is required for sustained activation of repeat enhancer-activated genes. Together, our findings reveal an epigenetic gatekeeper function of the ETV6 tumor suppressor gene and establish microsatellite enhancers as a key mechanism underlying the unique gene-expression program of ETV6-RUNX1+/- like B-ALL.
Evaluation of DNA adduct damage using G-quadruplex-based DNAzyme
Authors: Yi Xiao, Haomin Yi, Jingzhi Zhu, Suhua Chen, Guofang Wang, Yilong Liao, Yuanyuan Lei, Liyin Chen, Xingcai Zhang, Fangfu Ye
Journal: Bioactive Materials (2022)

Toxicity assessment is a major problem in pharmaceutical candidates and industry chemicals development. However, due to the lack of practical analytical methods for DNA adduct analysis, the safety evaluation of drug and industry chemicals was severely limited. Here, we develop a DNAzyme-based method to detect DNA adduct damage for toxicity assessment of drugs and chemicals. Among 18 structural variants of G4 DNAzyme, EA2 DNAzyme exhibits an obvious DNA damaging effect of styrene oxide (SO) due to its unstable structure. The covalent binding of SO to DNAzyme disrupts the Hoogsteen hydrogen bonding sites of G-plane guanines and affects the formation of the G4 quadruplex. DNA damage chemicals reduce the peroxidase activity of the G4 DNAzyme to monitor the DNA adduct damage by disrupting the structural integrity of the G4 DNAzyme. Our method for genotoxic assessment of pharmaceutical candidates and industrial chemicals can elucidate the complex chemical pathways leading to toxicity, predict toxic effects of chemicals, and evaluate possible risks to human health.
Immunotherapeutic Targeting and PET Imaging of DLL3 in Small-Cell Neuroendocrine Prostate Cancer
Authors: Jonathan Chou, Emily A. Egusa, Sinan Wang, Michelle L. Badura, Fei Lee, Anil P. Bidkar, Jun Zhu, Tanushree Shenoy, Kai Trepka, Troy M. Robinson, Veronica Steri, Jiaoti Huang, Yuzhuo Wang, Eric J. Small, Emily Chan, Bradley A. Stohr, Alan Ashworth, Brant Delafontaine, Sylvie Rottey, Keegan S. Cooke, Nooshin Hashemi Sadraei, Brian Yu, Mark Salvati, Julie M. Bailis, Felix Y. Feng, Robert R. Flavell, Rahul Aggarwal
Journal: Cancer Research (2022)

Abstract Effective treatments for de novo and treatment-emergent small-cell/neuroendocrine (t-SCNC) prostate cancer represent an unmet need for this disease. Using metastatic biopsies from patients with advanced cancer, we demonstrate that delta-like ligand 3 (DLL3) is expressed in de novo and t-SCNC and is associated with reduced survival. We develop a PET agent, [89Zr]-DFO-DLL3-scFv, that detects DLL3 levels in mouse SCNC models. In multiple patient-derived xenograft models, AMG 757 (tarlatamab), a half-life–extended bispecific T-cell engager (BiTE) immunotherapy that redirects CD3-positive T cells to kill DLL3-expressing cells, exhibited potent and durable antitumor activity. Late relapsing tumors after AMG 757 treatment exhibited lower DLL3 levels, suggesting antigen loss as a resistance mechanism, particularly in tumors with heterogeneous DLL3 expression. These findings have been translated into an ongoing clinical trial of AMG 757 in de novo and t-SCNC, with a confirmed objective partial response in a patient with histologically confirmed SCNC. Overall, these results identify DLL3 as a therapeutic target in SCNC and demonstrate that DLL3-targeted BiTE immunotherapy has significant antitumor activity in this aggressive prostate cancer subtype. Significance: The preclinical and clinical evaluation of DLL3-directed immunotherapy, AMG 757, and development of a PET radiotracer for noninvasive DLL3 detection demonstrate the potential of targeting DLL3 in SCNC prostate cancer.